Email updates

Keep up to date with the latest news and content from BMC Anesthesiology and BioMed Central.

Open Access Highly Accessed Research article

Population pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery

Wai Johnn Sam1, Gregory B Hammer2 and David R Drover1*

Author Affiliations

1 Department of Anesthesia, Stanford University, Stanford, California USA

2 Department of Anesthesia and Pediatrics, Stanford University, Stanford, California, USA

For all author emails, please log on.

BMC Anesthesiology 2009, 9:5  doi:10.1186/1471-2253-9-5

Published: 27 July 2009



The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).


We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.


The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44% and 21.6%, respectively.


Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 μg remifentanil followed by an infusion of 3.7 μg/min before, during and post-CPB, supplemented with a bolus dose of 25 μg given at the start of CPB.